A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

Abstract

Purpose The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnO SM20(−) ) NPs in Sprague Dawley rats for 90 days. Methods The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results No rats died during the test period. However, ZnO SM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion A ZnO SM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution.

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A review of hepatic nanotoxicology – summation of recent findings and considerations for the next generation of study designs

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“…Zinc oxide (ZnO) NMs are considered to exhibit relative rapid dissolution that contributes to the toxicity of nano-sized preparations. Oral exposure of negatively charged ZnO NMs (approximately 30 nm) in 5-week-old male and female Sprague-Dawley rats daily for 90 days (125, 250 or 500 mg/ kg) followed by a 14-day recovery period resulted in a dose-dependent accumulation in liver (up to 68.67 ng/g tissue) (Park et al 2014). Analysis of serum biochemistry showed a fall in total serum protein and albumin levels in male mice treated with the higher doses.…”